Hepatitis a and B Vaccination in the US

Hepatitis A and B Vaccination in the United States

MARTHA C. SANCHEZ, MD

44 46 EN ABSTRACT found in children and adolescents. Protective antibody lev- Use of hepatitis A vaccine is a main component of travel els appear to persist beyond 20 years in healthy individuals.1 vaccination practices. In the United States, fluctuations Twinrix® (manufactured by GlaxoSmithKline), a combined in the number of annual hepatitis A infections have oc- hepatitis A and hepatitis B vaccine, was first licensed bythe curred recently due to large outbreaks related to import- Food and Drug Administration (FDA) in 2001 on a 3-dose ed foods and urban transmission among homeless indi- schedule (0, 1, and 6 months) for vaccination of persons aged viduals, warranting consideration for wider local use of >18 years.4 The efficacy of Twinrix has been found to be hepatitis A vaccine. comparable with existing single antigen hepatitis vaccines Hepatitis B vaccine is indicated for all adults, and espe- at 1 month after completion of series. At an alternate 4-dose cially healthcare workers. Since 1992, it has been adminis- schedule, Twinrix doses can be administered at 0, 7, and tered at birth. A new novel hepatitis B vaccine given in two 21 to 30 days, followed by a dose at 12 months. This alter- doses one month apart is available and has increased efficacy nate dosing may be useful when vaccination with Twinrix in adults. This article reviews the complete administration has been initiated and travel or other potential exposure is of these hepatitis vaccines. anticipated before the second dose.5 KEYWORDS: hepatitis A, hepatitis B, immunizations, healthcare workers, heplisav-B Indications In 1999 the Advisory Committee on Immunization Practices (ACIP) recommended vaccination against hepatitis A routinely to children at age 12 to 23 months living in commu- HEPATITIS A nities with high rates of disease, which led to a 79% decline Hepatitis A virus (HAV) is a nonenveloped positive strand of cases in states with prior elevated rates in 2004 compared RNA virus, member of the Picornavirus family, that is to 1996.6 In 2006, ACIP extended the recommendation of mainly transmitted through fecal-oral route and exposure to routine hepatitis A vaccination to children nationwide. contaminated food and water sources. It commonly causes a Other groups advised for HAV vaccination due to increased self-limited inflammatory response in the liver that is asso- risk of exposure include: men who have sex with men (MSM), ciated with generalized symptomatology, but in rare cases users of injection and non-injection drugs, persons with it may progress to fulminant hepatitis and liver failure.1 clotting-factor disorders, persons with occupational risk of Although the average number of annual HAV infections infection, persons with chronic liver disease, persons travel- reported to the Centers for Disease Control (CDC) recently ing to or working in countries that have high or intermediate has declined substantially compared to the year 2000, fluc- hepatitis A endemicity.1 tuations have occurred in the last 20 years because of large Preexposure prophylaxis with hepatitis A vaccine is also outbreaks related to imported foods, people who use drugs, indicated for unvaccinated persons who are household experience homelessness and men who have sex with men.2 members and other close personal contacts of adopted children newly arriving from countries with high or intermedi- Vaccines ate hepatitis A.7 The first dose of the HAV vaccine should There are two licensed Hepatitis A antigen vaccines avail- be given ideally 2 or more weeks before the arrival of the able in the Unites States for individual 12 months and adoptee. For infants 6–11 months of age that are at increased older, HAVRIX® (manufactured by GlaxoSmithKline) and risk for HepA exposure, a single dose of HAV vaccine may VAQTA® (manufactured by Merck & Co., Inc). The schedule be given; this dosage will not be counted toward the routine for HAVRIX® is 0, 6–12 months and for VAQTA® 0, 6–18 2-dose series. months.3 Both vaccines provide high immunogenicity-in- Given the higher risk for HAV infection and severe infec- ducing protective antibody levels in 94%–100% of adults tion-associated outcomes in persons experiencing home- one month after the first dose, and 100% one month after lessness, in October 2018 the ACIP advised that all persons the second dose. Similar rates of neutralizing antibodies are aged 1 year and older in this group be routinely immunized

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against HAV.8 Immunity towards HAV in this population is and symptomatic disease. The primary infection is usually expected to reduce the risk of large-scale, person-to-person self-limited in immunocompetent adults, causing chronic outbreaks, but possible barriers to vaccination include lim- infection in about 5% but it may be as high as 30–90% in ited access to care and insurance coverage among persons children <5 years old. In the US, the rate of reported acute experiencing homelessness. hepatitis B virus infections declined 88.5% since recom- Post-exposure prophylaxis has been shown to be benefi- mendations for HepB vaccination were first issued, from 9.6 cial for persons exposed to HAV within a 2-week period; it is cases per 100,000 population in 1982 to 1.1 cases per 100,000 favored over the immunoglobulin due to induction of active population in 2015.12,13 immunity, longer duration of protection, ease of administration, and greater acceptability and availability.9 Vaccines Two single antigen vaccines against hepatitis B are avail- Adverse Effects able in the United States, Recombivax HB® (Merck & Co., Pain at the injection site (56%–67%), headache (14%–16%), Inc., Whitehouse Station, New Jersey) and Engerix-B® (Glaxo- and malaise (7%) are the most common side effects reported SmithKline Biologicals, Rixensart, Belgium). Either should in adults. No serious adverse events have been definitively be administered at 0, 1, and 6 months, but alternate sched- related to the hepatitis A vaccine.1 ule of 0, 2 and 4 months or 0, 1 and 4 months will provide similar response. After the first dose, 30–50% of healthy Contraindications adults will have protective antibody levels, 75% after the Hepatitis A vaccine should be avoided in those with a his- second dose and 90% after the third. An accelerated sched- tory of severe allergic reaction such as anaphylaxis to any ule may be given at 0, 7, and 21 days, followed by a booster component of the vaccine. at 12 months. The hepatitis B virus (HBV) vaccine after the completed vaccination series provides protection for about Pregnancy 20 years and possibly lifelong. The risk to the fetus when the vaccine is given during A combined inactivated hepatitis A and hepatitis B vac- pregnancy has not been determined; since the vaccine is cine (Twinrix, GlaxoSmithKline) is available for those 18 inactivated, it is suspected to be low.10 years and older to be given 0, 1 and 6 months or an accelerated schedule at 0,7, 21–30 days with a booster at 12 months. Safety On February 2018, Heplisav-B (HepB-CpG), a single- The vaccine may be given to immunocompromised patients, antigen HepB vaccine with a novel immunostimulatory since it is inactivated. In this population, efficacy may be sequence adjuvant was recommended for the prevention of lower depending on the degree of immunosuppression. HBV in persons aged ≥18 years. This vaccine is administered as 2 doses, 1 month apart, and has improved immunogenic- Hepatitis A Immunoglobulin ity with a similar safety profile to Engerix-B®.14,15 Seropro- GamaSTAN S/D is available in the United States, with rec- tective antibody to hepatitis B surface antigen (anti-HBs) ommended dosing of 0.1 mL/kg for up to 1 month of planned levels were achieved in 90.0%–100.0% of subjects receiv- travel duration and 0.2 mL/kg for up to 2 months has been ing 2 doses of HepB-CpG, compared with 70.5%–90.2% of shown to decrease HAV infection by 90%. It may be given, subjects receiving 3 dose series of Engerix-B. in conjunction to the HepA vaccine, at separate anatomic The same vaccine formulation should be used to complete sites, within 2 weeks potential exposure to HAV for: adults the series, although vaccination should not be deferred if aged >40 years, immunocompromised persons, those with same vaccine manufacturer is not available or unknown.16 chronic liver disease, or other chronic medical conditions. Persons may receive the hepatitis A immunoglobulin alone Indications if they are <12 months of age, are allergic to a component of HepB vaccination is universally indicated within 24 hours the vaccine or choose not to receive the vaccine.11 Immuno- of birth for medically stable infants weighing ≥2,000 grams. globulin cannot be administered simultaneously with MMR. In addition, routine vaccination is advised for unvaccinated children and adolescents aged <19 years, as well as adults at risk for HBV infection – all healthcare workers, sexual expo- HEPATITIS B sure to hepatitis B, history of current or recent injection drug Hepatitis B (HepB) is a DNA virus of the Hepadnavirus use, risk for infection by percutaneous or mucosal exposure family that is an important cause of chronic liver disease to blood, persons with chronic liver disease, persons with worldwide, which may lead to liver cirrhosis and hepato- human immunodeficiency virus infection, incarcerated per- cellular carcinoma. It is transmitted through percutaneous sons – and those requesting protection from HBV without or mucosal exposure to infectious blood or body fluids. The acknowledgment of a specific risk factor.17 liver is the main site of infection, causing asymptomatic International travelers to countries with high or

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intermediate levels of endemic HBV infection (HBsAg prev- 4. Centers for Disease Control and Prevention (CDC). FDA approval for a combined hepatitis A and B vaccine. MMWR Morb alence ≥2%) should be vaccinated against HBV, particularly Mortal Wkly Rep. 2001;50(37):806-807. healthcare workers, disaster relief personnel, receipt of med- 5. Notice to Readers: FDA Approval of an Alternate Dosing Sched- ical care, sexual activity, intravenous drug use, tattooing, ule for a Combined Hepatitis A and B Vaccine (Twinrix®). among others. JAMA. 2007;298(24):2863-2863. doi:10.1001/jama.298.24.2863 6. Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the Postvaccination serologic testing 1–2 months after the United States in the era of vaccination. JAMA. 2005;294(2):194- final dose of vaccine is recommended for certain persons 201. doi:10.1001/jama.294.2.194 following vaccination (e.g., hemodialysis patients, HIV-in- 7. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated recommenda- fected and other immunocompromised persons, healthcare tions from the Advisory Committee on Immunization Practices personnel, and sex partners of HBsAg-positive persons). (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Revaccination may consist of administration of a second Rep. 2009;58(36):1006-1007. complete HBV vaccine series using any of the available 8. Doshani M. Recommendations of the Advisory Committee on vaccines. Administration of more than two complete HBV Immunization Practices for Use of Hepatitis A Vaccine for Per- sons Experiencing Homelessness. MMWR Morb Mortal Wkly vaccine series is generally not recommended, except for Rep. 2019;68. doi:10.15585/mmwr.mm6806a6 17 hemodialysis patients. 9. Nelson NP. Update: Recommendations of the Advisory Com- mittee on Immunization Practices for Use of Hepatitis A Vac- cine for Postexposure Prophylaxis and for Preexposure Prophy- Adverse events laxis for International Travel. MMWR Morb Mortal Wkly Rep. Most common reported side effects are pain at the injection 2018;67. doi:10.15585/mmwr.mm6743a5 site >10%. Other reactions such as low-grade fever, myal- 10. Zhao Y, Jin H, Zhang X, Wang B, Liu P. Viral hepatitis vaccination during pregnancy. Hum Vaccines Immunother. 2016;12(4):894- gia, and headaches are rare (<1%). Mild adverse event, seri- 902. doi:10.1080/21645515.2015.1132129 ous adverse event, or cardiovascular event in subjects that 11. Nelson NP. Updated Dosing Instructions for Immune Glob- received HepB-CpG were 45.6%, 5.4%, and 0.27% compared ulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophy- laxis. MMWR Morb Mortal Wkly Rep. 2017;66(36):959-960. to subjects receiving Engerix-B, 45.7%, 6.3%, and 0.14%, doi:10.15585/mmwr.mm6636a5 14 respectively. 12. U.S. 2008 Surveillance Data for Acute Viral Hepatitis | Statis- tics & Surveillance | Division of Viral Hepatitis | CDC. https:// Contraindications www.cdc.gov/hepatitis/statistics/2008surveillance/index.htm. 13. WHO | Global hepatitis report, 2017. WHO. http://www.who. Hepatitis B vaccine should not be administered to those int/hepatitis/publications/global-hepatitis-report2017/en/. Ac- with a history of severe allergic reaction such as anaphylaxis cessed February 12, 2020. to yeast or any other component of the vaccine. 14. Hyer R, McGuire DK, Xing B, Jackson S, Janssen R. Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults. Vaccine. Pregnancy 2018;36(19):2604-2611. doi:10.1016/j.vaccine.2018.03.067 The vaccine contains a noninfectious hepatitis B surface 15. Sablan BP, Kim DJ, Barzaga NG, et al. Demonstration of safety and enhanced seroprotection against hepatitis B with investi- antigen and the risk to the fetus when the vaccine is given gational HBsAg-1018 ISS vaccine compared to a licensed hep- during pregnancy is low. There is limited human data of atitis B vaccine. Vaccine. 2012;30(16):2689-2696. doi:10.1016/j. vaccine-associated risks on HepB-CpG administered to vaccine.2012.02.001 16. ACIP General Best Practice Guidelines for Immunization|Recom- pregnant women. mendations|CDC. https://www.cdc.gov/vaccines/hcp/acip-recs/ general-recs/index.html. Published April 16, 2019. Accessed Immunoglobulin February 12, 2020. 17. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepa- HepB immunoglobulin may be administered in conjunc- titis B Virus Infection in the United States: Recommenda- tion with the hepatitis B vaccines in patients after high-risk tions of the Advisory Committee on Immunization Practices. MMWR Recomm Rep Morb Mortal Wkly Rep Recomm Rep. exposure with infected blood or body fluids within 24 hours 2018;67(1):1-31. doi:10.15585/mmwr.rr6701a1 of exposure. Author Martha C. Sanchez, MD, Assistant Professor of Medicine (Clinical), Division of Infectious Diseases, Alpert Medical School References of Brown University, Providence, RI. 1. Advisory Committee on Immunization Practices (ACIP), Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or Correspondence passive immunization: recommendations of the Advisory Com- Martha C. Sanchez, MD mittee on Immunization Practices (ACIP). MMWR Recomm 180 Corliss Street, Providence, RI 02904 Rep Morb Mortal Wkly Rep Recomm Rep. 2006;55(RR-7):1-23. 401-793-2928 2. Hepatitis A Outbreaks in the United States | CDC. https:// www.cdc.gov/hepatitis/outbreaks/hepatitisaoutbreaks.htm. [email protected] 3. Armstrong ME, Giesa PA, Davide JP, et al. Development of the formalin-inactivated hepatitis A vaccine, VAQTA from the live attenuated virus strain CR326F. J Hepatol. 1993;18 Suppl 2:S20- 26. doi:10.1016/s0168-8278(05)80373-3.

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